Certain 4-aryl-4-oxo butanoic acids are known to possess anti-inflammatory properties. Belgian Pat. No. 772,804. For example, the compound 4-biphenylyl-4-oxo butanoic acid ("fenbufen") has been used in the treatment of rheumatoid diseases. Similarly, monohalo derivatives of 4-biphenyl-4-oxo-2-methylbutanoic acid demonstrate short-lived anti-inflammatory activity. Swiss Pat. No. 628 014.
In comparison with the unsubstituted parent compound, a monotropoic halogen substitution on the outer aromatic ring of 4-biphenylyl-4-oxo butanoic acid results in a substantial decrease in, or even a total loss of anti-inflammatory action. R. G. Child et al., J. Pharm. Sci. Vol. 66 (1977), pp. 466-76. The reference teaches that the activity of fenbufen for Carrageenin edema is 1.9 and the percent inhibition for adjuvant arthritis is 71%. For 4'-Cl-fenbufen, there is no activity for Carrageenin edema and the percent inhibition for adjuvant arthritis is 61%. For 4'-F-fenbufen, the activity for Carrageenin edema is 1.7 and there is no activity for adjuvant arthritis. See, J. Pharm. Sci., Vol. 66 (1977), pp. 468-9, tabulated at I, II, and XXIX. Thus, the available literature suggests that a ditopic substitution by a chlorine or fluorine atom on the same benzene ring would lead to similar or even greater losses in anti-inflammatory activity.